Alpha-1 Antitrypsin Deficiency: Understanding the Genetic Cause of COPD and Current Treatments

Most people think COPD is caused by smoking. And while smoking is the biggest risk factor, there’s another cause many doctors miss - one you’re born with. Alpha-1 antitrypsin deficiency (AATD) is a genetic condition that silently destroys lungs and liver, often before age 40. It’s not rare. It’s just hidden.

What Exactly Is Alpha-1 Antitrypsin Deficiency?

Alpha-1 antitrypsin (AAT) is a protein made in your liver. Its job? To protect your lungs from damage. Every time your body fights infection, white blood cells release an enzyme called neutrophil elastase. That enzyme breaks down bad bacteria - but it can also tear up healthy lung tissue. AAT acts like a shield, stopping that enzyme from going too far.

In AATD, a faulty gene - called SERPINA1 - tells your liver to make a broken version of AAT. Instead of flowing into your bloodstream, the bad protein clumps up inside liver cells. That means your lungs get no protection. Over time, the unchecked enzyme eats away at the air sacs in your lungs, leading to emphysema. That’s why AATD causes COPD - even in non-smokers.

The most common bad version is the Z allele. If you inherit two copies (ZZ), your AAT levels drop to 15% of normal. That’s when serious lung and liver damage starts. About 1 in 2,000 to 1 in 5,000 people carry this. But here’s the kicker: only 10% of them know it.

Why Is It So Often Missed?

Patients with AATD usually show up at the doctor with coughing, wheezing, and trouble breathing. Sounds like asthma or regular COPD, right? So they’re treated for that. But if you’re under 45, have no smoking history, and your lungs are worse in the lower parts (basilar emphysema), that’s a red flag.

Studies show it takes an average of 8 years and three different doctors before someone with AATD gets the right diagnosis. Many end up being told they have "chronic bronchitis" or "tough asthma" for years. One patient on a support forum said, "I was on inhalers for 12 years before someone finally checked my AAT levels. That’s 12 years of unnecessary damage."

The problem isn’t just the symptoms. It’s the system. Most primary care doctors don’t test for AATD unless someone has a family history - and even then, it’s rare. The American Thoracic Society and European Respiratory Society say everyone diagnosed with COPD, asthma with fixed airflow blockage, or unexplained liver disease should be tested. But only a fraction are.

How Is It Diagnosed?

There are two simple tests. First, a blood test checks your AAT level. If it’s below 50 mg/dL, that’s abnormal. Then comes the second step: genotyping. This tells you exactly which gene variants you carry - MM (normal), MZ (carrier), or ZZ (severe deficiency).

Phenotyping - a more detailed test that looks at the protein shape - is sometimes used too. It’s slower and more expensive, but it catches rare variants. The whole process usually takes 2 to 6 weeks, depending on the lab.

Testing is free or low-cost in many places if your doctor orders it. But many don’t know to order it. If you’ve been diagnosed with COPD before age 45, have a family member with lung or liver disease, or have unexplained liver problems, ask for the test. It takes one blood draw. It could change everything.

What Happens When You Have It?

People with ZZ genotype have a 75% chance of developing lung disease by age 60 - if they smoke. If they don’t? That risk drops dramatically. Smoking isn’t just a risk factor - it’s a multiplier. One study found quitting smoking at diagnosis could reduce lung damage by up to 60%.

Liver damage is less predictable. Some babies with ZZ develop jaundice and liver failure. Others never have liver issues. But by age 50, up to 40% of ZZ adults show signs of liver scarring. A small number go on to develop cirrhosis or even liver cancer. That’s why regular liver scans and blood tests are part of long-term care.

There’s also a rare skin condition called panniculitis - painful lumps under the skin - that can appear in a few cases. It’s not common, but if you have it and no other explanation, AATD should be ruled out.

What Treatments Are Available?

There’s no cure. But there’s a treatment that helps your lungs: augmentation therapy. It’s simple in theory - you get weekly IV infusions of purified human AAT. This raises your blood levels above the protective threshold of 11 μM, which slows lung damage.

Three FDA-approved products are used in the U.S.: Prolastin-C, Zemaira, and Aralast NP. Each costs between $70,000 and $100,000 a year. Insurance often denies the first claim - but appeals work. A 2022 review found 42% of initial requests were rejected, but 78% were approved after doctor appeals.

There’s good news: in 2022, the FDA approved the first subcutaneous (under-the-skin) version. It’s less invasive than IV infusions. You can do it yourself at home. It’s not available everywhere yet, but it’s coming.

For liver damage? There’s no drug that fixes the misfolded protein. If cirrhosis gets bad, a liver transplant is the only option. That’s why early diagnosis matters so much - catching it before the liver is destroyed gives you time to avoid the worst.

What About New Treatments on the Horizon?

Scientists aren’t waiting. Several new therapies are in trials. One approach uses RNA interference to silence the faulty gene in the liver - stopping the bad protein from being made at all. Another uses small molecules to help the protein fold correctly, so it can escape the liver and reach the lungs.

Gene therapy is also being tested. The goal? Insert a healthy copy of the SERPINA1 gene into your cells so your body starts making normal AAT. Early results look promising.

And then there’s newborn screening. Twelve U.S. states now test babies for AATD as part of routine screening. That means kids with ZZ can be identified before symptoms start. They can be told to avoid smoking, get regular lung checks, and maybe even get treatment before damage begins. That’s a game-changer.

What Should You Do If You Have It?

First: stop smoking. Immediately. If you vape, quit that too. No exceptions. Second: get vaccinated. Flu, pneumonia, and COVID-19 shots are critical - your lungs can’t afford extra stress.

Third: get tested. If you have AATD, your siblings, children, and parents should be tested too. It’s inherited. You might be the first in your family to know - but you’re not the only one at risk.

Fourth: see a specialist. A pulmonologist who knows AATD. A genetic counselor. A hepatologist if your liver is affected. This isn’t something to manage alone.

Fifth: join a support group. The Alpha-1 Foundation connects patients with others who get it. You’ll learn about clinical trials, insurance tips, and how to handle the emotional toll. One man in his 50s said, "Knowing I’m not alone - and that my kids won’t have to go through what I did - made all the difference."

Why This Matters Beyond You

AATD is a mirror. It shows us that not all COPD is the same. It reminds us that genetics matter - even in diseases we think are purely environmental. And it proves that early detection saves lives.

Right now, 25,000 to 30,000 Americans with severe AATD don’t know they have it. That’s 25,000 people getting the wrong treatment, losing lung function, and possibly developing liver disease - all because no one thought to test.

If you’re a doctor, test your COPD patients. If you’re a patient with unexplained lung disease, ask for the test. If you’re a family member of someone with COPD or liver disease, get screened. This isn’t about hype. It’s about stopping a silent killer before it’s too late.